Rapid and accurate detection of cinnamon oil adulteration in perilla leaf oil using atmospheric solids analysis probe-mass spectrometry.

Perilla leaf oil (PLO) is a global premium vegetable oil with abundant nutrients and substantial economic value, rendering it susceptible to potential adulteration by unscrupulous entrepreneurs. The addition of cinnamon oil (CO) is one of the main adulteration avenues for illegal PLOs. In this study, new and real-time ambient mass spectrometric methods were developed to detect CO adulteration in PLO. First, atmospheric solids analysis probe tandem mass spectrometry combined with principal component analysis and principal component analysis-linear discriminant analysis was employed to differentiate between authentic and adulterated PLO. Then, a spectral library was established for the instantaneous matching of cinnamaldehyde in the samples. Finally, the results were verified using the SRM mode of ASAP-MS/MS. Within 3 min, the three methods successfully identified CO adulteration in PLO at concentrations as low as 5% v/v with 100% accuracy. The proposed strategy was successfully applied to the fraud detection of CO in PLO.

Enhanced VOC emission with increased temperature contributes to the shift of O3-precursors relationship and optimal control strategy.

Assessing the impact of anthropogenic volatile organic compounds (VOCs) on ozone (O3) formation is vital for the management of emission reduction and pollution control. Continuous measurement of O3 and the major precursors was conducted in a typical light industrial city in the YRD region from 1 May to 25 July in 2021. Alkanes were the most abundant VOC group, contributing to 55.0% of TVOCs concentration (56.43 ± 21.10 ppb). OVOCs, aromatics, halides, alkenes, and alkynes contributed 18.7%, 9.6%, 9.3%, 5.2% and 1.9%, respectively. The observational site shifted from a typical VOC control regime to a mixed regime from May to July, which can be explained by the significant increase of ROx production, resulting in the transition of environment from NOx saturation to radical saturation with respect to O3 production. The optimal O3 control strategy should be dynamically changed depending on the transition of control regime. Under NOx saturation condition, minimizing the proportion of NOx in reduction could lead to better achievement of O3 alleviation. Under mixed control regime, the cut percentage gets the top priority for the effectiveness of O3 control. Five VOCs sources were identified: temperature dependent source (28.1%), vehicular exhausts (19.9%), petrochemical industries (7.2%), solvent & gasoline usage (32.3%) and manufacturing industries (12.6%). The increase of temperature and radiation would enhance the evaporation related VOC emissions, resulting in the increase of VOC concentration and the change of ROx circulation. Our results highlight determination of the optimal control strategies for O3 pollution in a typical YRD industrial city.

Genome-wide identification of the histone modification gene family in Aquilaria sinensis and functional analysis of several HMs in response to MeJA and NaCl stress.

Histone modifications (HMs) play various roles in growth, development, and resistance to abiotic stress. However, HMs have been systematically identified in a few plants, and identification of HMs in medicinal plants is very rare. Aquilaria sinensis is a typical stress-induced medicinal plant, in which HMs remain unexplored. We conducted a comprehensive study to identify HMs and obtained 123 HMs. To conduct evolutionary analysis, we constructed phylogenetic trees and analyzed gene structures. To conduct functional analysis, we performed promoter, GO, and KEGG analyses and ortholog analyses against AtHMs. Based on the expression profiles of different tissues and different layers of Agar-Wit, some HMs of A. sinensis (AsHMs) were predicted to be involved in the formation of agarwood, and their response to MeJA and NaCl stress was tested by qRT-PCR analysis. By analyzing the enrichment of H3K4me3, H3K27me3, and H4K5ac in the promoter regions of two key sesquiterpene synthase genes, AsTPS13/18, we hypothesized that AsHMs play important roles in the synthesis of agarwood sesquiterpenes. We confirmed this hypothesis by conducting RNAi transgenic interference experiments. This study provided valuable information and important biological theories for studying epigenetic regulation in the formation of agarwood. It also provided a framework for conducting further studies on the biological functions of HMs.

Effect of Polygonatum sibiricum on biological toxicity of zinc oxide nanoparticles during respiratory exposure.

Although zinc oxide nanoparticles (ZnO NPs) with distinct physicochemical properties have attracted great attention, the application of ZnO NPs is still limited due to their potential biotoxicity. In this work, ZnO-Polygonatum sibiricum (PS) NPs are synthesized to overcome this challenge. The ZnO NPs stably combine with PS according to microstructural observation, particle size distribution, zeta potential results and Fourier transform infrared spectroscopy analysis. The cytotoxicity of ZnO NPs is alleviated by combining them with PS as a consequence of the diminished generation of reactive oxygen species and reinforced superoxide dismutase activity. Furthermore, the respiratory index and histopathologic results of mice exposed to NPs manifest that the pulmonary dysfunction caused by ZnO NPs is avoided in the ZnO-PS NPs group. This study provides the foundations for the amelioration and universal utilization of ZnO NPs and emphasizes the potential of ZnO-PS NPs in biomedical applications.

Anti-inflammatory effects of Tao Hong Si Wu Tang in mice with lung cancer and chronic obstructive pulmonary disease.

BACKGROUND: Lung cancer (LC) combined with chronic obstructive pulmonary disease (COPD) is a common combination of comorbidities. Anti-inflammation and modulation of oxidative/antioxidative imbalance may prevent COPD-induced LC, and are also crucial to the treatment of LC combined with COPD. Modern studies have shown that Tao Hong Si Wu Tang (THSW) has vasodilatory, anti-inflammatory, anti-fatigue, anti-shock, immunoregulatory, lipid-reducing, micronutrient-supplementing, and anti-allergy effects. AIM: To observe the effects of THSW on COPD and LC in mice. METHODS: A total of 100 specific pathogen-free C57/BL6 mice were randomly divided into five groups: Blank control group (group A), model control group (group B), THSW group (group C), IL-6 group (group D), and THSW + IL-6 group (group E), with 20 mice in each group. A COPD mouse model was established using fumigation plus lipopolysaccharide intra-airway drip, and an LC model was replicated by in situ inoculation using the Lewis cell method. RESULTS: The blank control group exhibited a clear alveolar structure. The model control and IL-6 groups had thickened alveolar walls, with smaller alveolar lumens, interstitial edema, and several inflammatory infiltrating cells. Histopathological changes in the lungs of the THSW and THSW + IL-6 groups were less than those of the model control group. The serum IL-1ß, IL-6, and TNF-α levels and IL-6R, JAK, p-JAK, STAT1/3, p-STAT1/3, FOXO, p-FOXO, and IL-7R expression levels in lung tissues of mice in the rest of the groups were significantly higher than those of the blank control group (P < 0.01). Compared with the model control group, the IL-6 group demonstrated significantly higher levels for the abovementioned proteins in the serum and lung tissues (P < 0.01), and the THSW group had significantly higher serum IL-1ß, IL-6, and TNF-α levels and IL-7R expression levels in lung tissues (P < 0.01) but significantly decreased IL-6R, JAK, p-JAK, STAT1/3, p-STAT1/3, FOXO, p-FOXO, and IL-7R levels (P < 0.01). CONCLUSION: THSW reduces the serum IL-1ß, IL-6, and TNF-α levels in the mouse model with anti-inflammatory effects. Its anti-inflammatory mechanism lies in inhibiting the overactivation of the JAK/STAT1/3 signaling pathway.

ZIP Code and ZIP Code Tabulation Area Linkage: Implications for Bias in Epidemiologic Research.

BACKGROUND: To our knowledge, no agreed-upon best practices exist for joining U.S. Census ZIP Code Tabulation Areas (ZCTAs) and U.S. Postal Service ZIP Codes (ZIPs). One-to-one linkage using 5-digit ZCTA identifiers excludes ZIPs without direct matches. "Crosswalk" linkage may match a ZCTA to multiple ZIPs, avoiding losses. METHODS: We compared non-crosswalk and crosswalk linkages nationally and for mortality and health insurance in California. To elucidate selection implications, generalized additive models related sociodemographics to whether ZCTAs contained non-matching ZIPs. RESULTS: Nationwide, 15% of ZCTAs had non-matching ZIPs, i.e., ZIPs dropped under non-crosswalk linkage. ZCTAs with non-matching ZIPs were positively associated with metropolitan core location, lower socioeconomics, and non-white population. In California, 34% of ZIPs in the mortality and 25% in the health insurance data had ZCTAs with non-matching ZIPs; however, these ZIPs constitute only 0.03% of total mortality and 0.44% of total insurance enrollees. CONCLUSIONS: Our study findings support the use of crosswalk linkages and ZCTAs as a unit of analysis. One-to-one linkage may cause bias by differentially excluding ZIPs with more disadvantaged populations, although affected population sizes appear small.

Calcium silicate cements endowing bioactivity and sustaining mechanical strength of low-heat-releasing and fast-curing magnesium phosphate cements.

It is known that magnesium phosphate cements (MPCs) show appreciable mechanical strength and biocompatibility, but the hydration reaction processes often lead to intense heat release while the hydration products present weak resistance to mechanical decay and low bioactivity. Herein we developed an MPC-based system, which was low-heat-releasing and fast-curing in this study, by compounding with self-curing calcium silicate cements (CSCs). The MPC composed of magnesium oxide (MgO), potassium dihydrogen phosphate (KH2PO4), disodium hydrogen phosphate (Na2HPO4), magnesium hydrogen phosphate trihydrate (MgHPO4·3H2O) and chitosan were weakly basic, which would be more stable in vivo. The physicochemical properties indicated that the addition of CSCs could increase the final setting time while decrease the heat release. Meanwhile, the CSCs could endow MPC substrate with apatite re-mineralization reactivity, especially, which add 25 wt.% CSCs showed the most significant apatite deposition. What's more, the mechanical evolution in buffer demonstrated CSCs could enhance and sustain the mechanical strength during degradation, and the internal constructs of cement implants could still be reconstructed by µCT analysis in rabbit femoral bone defect model in vivo. Particularly, appropriate CSCs adjusted the biodegradation and promoted new bone tissue regeneration in vivo. Totally, the MPC/CSCs composite system endows bioactivity and sustains mechanical strength of the MPC, which may be promising for expending the clinical applications of MPC-based bone cements.

Reshaped commensal wound microbiome via topical application of Calvatia gigantea extract contributes to faster diabetic wound healing.

Background: Calvatia gigantea (CG) is widely used as a traditional Chinese medicine for wound treatment. In this study, we aimed to determine the effects of CG extract (CGE) on diabetic wound healing and the commensal wound microbiome. Method: A wound model was established using leptin receptor-deficient db/db mice, with untreated mice as the control group and CGE-treated mice as the treatment group. The wound healing rate, inflammation and histology were analyzed. Additionally, wound microbiome was evaluated via 16S ribosomal RNA (rRNA) gene sequencing. Results: CGE significantly accelerated the healing of diabetic ulcer wounds, facilitated re-epithelialization, and downregulated the transcription levels of the inflammatory cytokines, interleukin-1ß and tumor necrosis factor-α. Furthermore, CGE treatment positively affected the wound microbiome, promoting diversity of the microbial community and enrichment of Escherichia-Shigella bacteria in the CGE-treated group. Conclusions: Overall, CGE enhanced diabetic wound healing by modulating the wound microbiome and facilitating macrophage polarization during inflammation. These findings suggest modulation of the commensal wound microbiome using medicinal plants as a potential therapeutic strategy for diabetic wounds.

Anticoagulation for the Prevention of Arterial Thromboembolism in Cancer Patients by Primary Tumor Site: A Systematic Review and Meta-Analysis of Randomized Trials.

AIMS: Incidence of arterial thromboembolism (ATE) among ambulatory cancer patients varies by primary tumor site. However, it is unclear whether this alters the benefit-to-harm profile of prophylactic anticoagulation for ATE prevention. Therefore, we systematically evaluated the efficacy and safety of anticoagulants for ATE prevention among ambulatory cancer patients according to the primary tumor site. METHODS AND RESULTS: We conducted a systematic review using Medline, Embase, SCOPUS, and CENTRAL, and included randomized trials comparing prophylactic anticoagulation to no anticoagulation among ambulatory cancer patients who initiated tumor-directed systemic therapy. Incidence of symptomatic ATE (acute ischemic stroke, acute myocardial infarction or peripheral artery occlusion) and major bleeding, as well as risk differences (RDs) attributable to anticoagulation were meta-analyzed by primary tumor site using random-effects modeling. We included 10 randomized controlled trials with 9,875 patients with follow-up ranging from 3.3 to 68 (median 6.6) months. While prophylactic anticoagulation did not reduce ATE risks overall (RD -0.49%; 95% CI -0.49% to 0.01%; I2=0%), it conferred a protective effect among pancreatic cancer patients (RD -3.2%; 95%CI -5.7% to -0.8%; I2=0%) without a detectable increase in major bleeding (RD -1.4%; 95% CI -4.6% to 1.8%; I2=0%). Prophylactic anticoagulation was not associated with ATE risk reduction in other tumor sites. CONCLUSION: Based on available evidence, prophylactic anticoagulation did not reduce ATE risk among ambulatory cancer patients overall. However, we observed lower incidence of ATE among pancreatic cancer patients randomized to receive anticoagulation. Prophylactic anticoagulant use to reduce ATEs in pancreatic cancer should be evaluated in future research.

Association of systemic immune-inflammation index with malnutrition among Chinese hospitalized patients: a nationwide, multicenter, cross-sectional study.

Background: Systemic immune-inflammation index (SII) is associated with increased risk in a wide range of illnesses. However, few studies have explored the associations between SII and the risk of malnutrition. Therefore, this study aimed to investigate the association between SII and malnutrition in a nationwide, multicenter, cross-sectional study involving Chinese hospitalized patients. Design: From August 2020 to August 2021, a total of 40,379 hospitalized patients met the inclusion and exclusion criteria. Detailed demographic data, diagnoses, as well as physical and laboratory examination results were recorded. The diagnosis of malnutrition was used with two distinct methods: the Malnutrition Screening Tool 2002 (NRS 2002) + Global Leaders Initiative on Malnutrition (GLIM) criteria and the controlling nutritional status (CONUT) score. The risk factors for malnutrition were analyzed using binary logistic regression and multiple logistic regression to obtain odds ratios (OR) and 95% confidence intervals (CI). Restricted cubic spline (RCS), linear spline, and receiver operating characteristic (ROC) analysis were also used. Results: The prevalence of malnutrition diagnosed by the two methods was 13.4% and 14.9%, respectively. In the NRS 2002 + GLIM diagnostic model, lnSII showed statistical significance between the malnutrition and non-malnutrition group (6.28 ± 0.78 vs. 6.63 ± 0.97, p < 0.001). A positive association was observed between higher SII and the risk of malnutrition in both before and after adjustment models compared to the first quartile (Q3 vs. Q1, OR = 1.27, 95%CI: 1.15-1.40; Q4 vs. Q1, OR = 1.83, 95%CI: 1.67-2.00). However, a significant reduction in prevalence was observed when SII was in the second quartile (Q2 vs. Q1, OR < 1), as indicated by a restricted cubic spline with a U trend (p for nonlinear <0.001). According to the CONUT score, the prevalence of individuals with normal nutritional status decreased with increasing SII, while the occurrence of three different degrees of malnutrition generally increased. The Kappa value between the two diagnostic methods was 0.23, and the merged data observed an area under the ROC curve of 0.73 (95%CI: 0.714-0.742). Conclusion: The U-shaped association between SII and the prevalence of malnutrition was observed. Both lower and higher SII levels (either continuous or categorical variable) were significantly associated with an increased risk of malnutrition.

The causal relationship between the gut microbiota and acute pancreatitis: A 2-sample Mendelian randomization study.

Several observational studies have reported a correlation between the gut microbiota (GM) and the risk of acute pancreatitis (AP). However, the causal relationship between them remains uncertain. We conducted a 2-sample Mendelian randomization (MR) study using pooled data from genome-wide association studies of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla) and AP patients. We evaluated the causal relationship between the GM and AP using methods such as inverse-variance weighting, MR-Egger, weighted medians, simple mode, and weighted mode. Cochran Q test, MR-Egger regression intercept analysis, and MR-PRESSO were used to examine the heterogeneity, multipotency, and outlier values of the variables, respectively. The reverse causal relationship between AP and the GM was assessed with reverse MR. In total, 5 gut microbial taxa were significantly associated with AP. The inverse-variance weighting results indicated that Acidaminococcaceae (odds ratio [OR]: 0.81, 95% confidence interval [CI]: 0.66-1.00, P = .045) and Ruminococcaceae UCG004 (OR: 0.85, 95% CI: 0.72-0.99, P = .040) were protective factors against the occurrence of AP. Coprococcus 3 (OR: 1.32, 95% CI: 1.03-1.70, P = .030), Eisenbergiella (OR: 1.13, 95% CI: 1.00-1.28, P = .043), and the Eubacterium fissicatena group (OR: 1.18, 95% CI: 1.05-1.33, P = .006) were risk factors for the development of AP. A comprehensive sensitivity analysis proved our results to be reliable. Reverse MR analysis did not indicate any causal relationship between AP and the GM. This study revealed a complex causal relationship between 5 GM taxa and AP, providing new insights into the diagnostic and therapeutic potential of the GM in AP patients.

Correlation of glucose and lipid metabolism, renal function and retinopathy in diabetic retinopathy patients using OCTA detection.

OBJECTIVE: To investigate the correlation between glucose and lipid metabolism, renal function, and retinopathy in patients with diabetic retinopathy (DR) based on optical coherence tomography angiography (OCTA). METHODS: A total of 584 diabetic patients who underwent treatment at The Second Affiliated Hospital of Dalian Medical University from March 2022 to June 2023 were retrospectively selected as research participants. They were categorized into a NDR group (n=366) and a DR group (n=218) based on the presence or absence of DR. Relevant indexes of glucose and lipid metabolism, renal function, and OCTA findings were collected. Logistic regression analysis was applied to identify the influencing factors of diabetes mellitus complicated with DR. ROC curves were drawn to examine the diagnostic value of the screened influencing factors for diabetes mellitus complicated with DR. Finally, Spearman correlation coefficients were calculated to examine the relevance between influencing factors and the severity of DR Lesions. RESULTS: Logistic regression showed that high levels of angiography 3 × 3 inner vascular density (IVD_33) and angiography 3 × 3 inner perfusion density (IPD_33) were protective factors for diabetes mellitus complicated with DR, and diabetic peridiabetic vascular disease (DPVD), elevated blood urea nitrogen (BUN), and urea levels were risk factors for diabetes mellitus complicated with DR (all P<0.05). ROC curve displayed that the areas under the curve (AUC) of IVD_33, DPVD, BUN, IPD_33, and Urea in predicting diabetes mellitus with DR were 0.779, 0.705, 0.621, 0.723, and 0.632, respectively. The AUC of combined prediction with OCTA index was higher than that of combined prediction without OCTA index (0.781 VS 0.84, P<0.05). Spearman correlation coefficient displayed that IVD_33 and IPD_33 were negatively correlated with the severity of DR, whereas DPVD and Urea showed a positive correlation (P<0.05). CONCLUSION: Our findings provide valuable insights for the initial clinical assessment of diabetic patients with DR and aid in the early determination of DR severity. Corresponding intervention measures should be formulated as early as possible to remedy patients' outcomes.

Effects of heterotrophic Euglena gracilis powder on dough microstructure, rheological properties, texture, and nutritional composition of steamed bread.

This study investigated the effects of incorporating different levels of Euglena gracilis microalgae powder (MP) on the dough properties, rheology, and quality attributes of Chinese steamed bread (CSB) for the first time. Moderate levels of MP (2%) reinforced the gluten network and improved protein structure, while higher levels (4-8%) adversely affected the gluten network and rheological properties. The addition of MP decreased the specific volume, pore number, and pore density of CSB, but increased pore size, hardness, and chewiness. It also imparted a yellow color to the CSB and slowed down moisture loss during storage. Notably, MP effectively increased the protein and lipid content of CSB, enhancing its nutritional value. The results suggest that optimizing the MP level is crucial to achieve nutritional enhancement while maintaining desirable texture and sensory attributes. An addition of 2% MP can strike a balance between nutrition and the overall quality of the final product.

Effective hydrogen production and coupling degradation of organics (4-nitrophenol, methylene blue, and Rhodamine B) in wastewater by electrospun PAN@Fe0 composite nanofibers.

The pursuit of clean energy generation and environmental preservation is of utmost importance for societal progress. However, couple clean energy production and pollution control is still a difficulty. In this study, a novel electrospun composite mat, with nano zero valent iron (Fe0, nZVI) encapsulated into polyacrylonitrile (PAN) nanofibers was acted as a catalyst. The activation energy (Ea) for the hydrolysis of NaBH4 to produce hydrogen is 22 kJ·mol-1, hydrogen atom utilization efficiency (HGE) of NaBH4 is 60.80%. Three kinds of organic dyes 4-nitrophenol (4-NP), methylene blue (MB), and Rhodamine B (RhB) were served as the model pollutant, to construct NaBH4-organic system for energy production and pollution reduction. The NaBH4-organic system demonstrates a collaborative capability to simultaneously remove organic pollutants and generate hydrogen, with a coupling equilibrium point between the two processes. The hydrogen generation rate (HGR) and HGE increased with the concentration of pollutants increased. The degradation of 4-NP, MB, and RhB followed pseudo-first-order kinetics, with RhB degrading dosage 20 and 44 times higher than 4-NP and MB, respectively. H2 and H· contributed to the organic degradation. nZVI directly participated in the formation H2 and H·. PAN@Fe0 possessed good recyclability and moderate cost. The degradation process adhered to the classical surface reaction controlled Langmuir-Hinshelwood (L-H) model. The integration of synergistic production capacity and pollutant degradation aligns well with the principles of green chemistry and sustainable development. This study demonstrates a novel approach to no precursor loss catalysts preparation, efficient production clean H2, advanced treatment of dye-containing wastewater, carbon neutral operation of sewage treatment plant.

The Diagnostic and Therapeutic Value of Anti CCP Antibodies and Double Stranded DNA in Rhupus Syndrome.

BACKGROUND: There have been only few reports on Rhupus syndrome with severe visceral involvement. Moreover, there was little consensus regarding its treatment. Belimumab is one of the options for treating this disease. For patients with clinical symptoms and elevated levels of anti CCP antibodies and anti-double stranded DNA antibodies, and it suggests Rhupus syndrome. After effective treatment, the decrease in levels of anti CCP antibodies and anti-double stranded DNA (ds-DNA) antibodies can effectively delay the progression of the disease and protect target organs. METHODS: We used a chemiluminescence instrument, (Yahuilong; Shenzhen, China), to measure the changes in CCP and dsDNA before and after treatment. RESULTS: Prior to treatment, the patient presented with symptoms of rheumatoid arthritis and systemic lupus erythematosus. Her laboratory tests showed dsDNA (214 IU/mL) and CCP level of ˃ 3,000 U/mL. After treatment with belimumab, the clinical symptoms were significantly relieved, and the patient's CCP IgG level decreased to 263.5 U/mL. A blood test found that her anti-dsDNA was negative. CONCLUSIONS: CCP and dsDNA can serve as indicators for the diagnosis and treatment of Rhupus syndrome.

Exploring the influence of different enzymes on soy hull polysaccharide emulsion stabilization: A study on interfacial behavior and structural changes.

The interfacial behavior of soy hull polysaccharide (SHP) at the oil-water interface and the stabilization mechanism of high internal phase emulsion (HIPE) with three enzymes (α-amylase, trypsin and papain) were investigated. The diameter of the α-amylase-treated emulsion was the minimum at 40 min, indicating that the carbohydrate portions of SHP form a thick layer on the surface of the droplet to prevent aggregation. Moreover, Raman spectroscopy revealed significantly higher levels of disordered content of SHP emulsion treated with α-amylase at 60 min, potentially affecting the directional movement of SHP molecules in the emulsion. Conversely, the content of ß-sheet and ß-turn was lower than trypsin and papain, possibly due to ion-dipole interaction between the polar group residues within SHP and ions, or protonation with H+.

Water-soluble and predictable-release triptolide prodrugs block bleomycin-induced pulmonary fibrosis in mice.

Idiopathic pulmonary fibrosis (IPF) is a progressive respiratory disease with no known cause. It is characterized by widespread inflammation and structural abnormalities in the alveoli of the lungs, ultimately leading to the development of pulmonary fibrosis. Triptolide (TP), an epoxy-diterpene lactone compound known for its potent anti-inflammatory and antifibrotic effects, was limited clinical use due to poor water solubility and side effects. Two soluble TP prodrugs (PG490-88 and Minnelide) have entered clinical research. However, their activities are based on enzyme metabolism, which is influenced by species-specific differences. In this study, we present water-soluble TP derivatives synthesized by introducing ethylenediamine carbamate groups (TP-DEAs) at the 14-hydroxy position. The introduced groups were found to spontaneously convert into the parent drug through enzyme-independent metabolic conversion. The water solubility and stability of the compounds were examined in vitro. Notably, TP-DEA2 exhibited high water solubility (30.8 mg/mL), exceeding TP solubility by more than 1181-fold. In vitro, TP-DEA2 converted to TP autonomously without the involvement of enzymes. In addition, TP-DEA2 can inhibit the expression of a disintegrin and metalloproteinase 10 (ADAM 10) induced by TGF-ß1 and reduce the secretion of a-SMA in fibroblasts. In vivo, TP-DEA2 transformed into TP, effectively inhibiting fibrosis in the bleomycin group without observed toxicity. Importantly, positive outcomes when administering TP-DEA2 at a later stage post-bleomycin exposure suggest its potential role in treating IPF.

Dose-response relationship between body mass index and hypertension: A cross-sectional study from Eastern China.

Background: A high body mass index (BMI) increases the risk of hypertension. However, little is known about the dose-dependent association between BMI and hypertension. Therefore, this study investigated the prevalence of hypertension in 7568 subjects from the Jiangsu Province, Eastern China, and analyzed the dose-response relationship between BMI and hypertension risk. Methods: The eligible subjects completed a structured questionnaire and clinical biochemical indicators were measured according to standardized protocols. Multivariate logistic regression models were used to evaluate the association between BMI and hypertension. Restricted cubic spline (RCS) analysis was used to analyze the dose-response relationship between BMI and hypertension risk. Moreover, sensitivity analysis was performed to verify the robustness of our findings. Results: The prevalence of hypertension was 35.3 % in the total population. BMI was significantly associated with systolic and diastolic blood pressure. The fully-adjusted odds ratio (OR) with 95 % confidence interval (CI) for hypertension was 1.17 (1.15, 1.19) for every 1 kg/m2 increase in BMI. Furthermore, the OR (95 % CI) for hypertension in the highest BMI group (Obesity) was 4.14 (3.45, 4.96) after adjusting for covariates compared with the normal group. Multivariable adjusted RCS analysis showed a positive and linear dose-response relationship between BMI and hypertension risk both in male and female populations (all P for non-linearity > 0.05). Conclusion: Our study demonstrated a positive and linear dose-response relationship between BMI and the risk of hypertension. The results of this study provide evidence for BMI-related clinical interventions to reduce the risk of hypertension.

Single-cell RNA sequencing highlights the immunosuppression of IDO1+ macrophages in the malignant transformation of oral leukoplakia.

Rationale: Immunosuppressive tumor microenvironment (iTME) plays an important role in carcinogenesis, and some macrophage subsets are associated with iTME generation. However, the sub-population characterization of macrophages in oral carcinogenesis remains largely unclear. Here, we investigated the immunosuppressive status with focus on function of a macrophage subset that expressed indoleamine 2,3 dioxygenase 1 (Macro-IDO1) in oral carcinogenesis. Methods: We built a single cell transcriptome atlas from 3 patients simultaneously containing oral squamous cell carcinoma (OSCC), precancerous oral leukoplakia (preca-OLK) and paracancerous tissue (PCA). Through single-cell RNA sequencing and further validation using multicolor immunofluorescence staining and the in vitro/in vivo experiments, the immunosuppressive cell profiles were built and the role of a macrophage subset that expressed indoleamine 2,3 dioxygenase 1 (Macro-IDO1) in the malignant transformation of oral leukoplakia was evaluated. Results: The iTME formed at preca-OLK stage, as evidenced by increased exhausted T cells, Tregs and some special subsets of macrophages and fibroblasts. Macro-IDO1 was predominantly enriched in preca-OLK and OSCC, distributed near exhausted T cells and possessed tumor associated macrophage transformation potentials. Functional analysis revealed the established immunosuppressive role of Macro-IDO1 in preca-OLK and OSCC: enriching the immunosuppression related genes; having an established level of immune checkpoint score; exerting strong immunosuppressive interaction with T cells; positively correlating with the CD8-exhausted. The immunosuppression related gene expression of macrophages also increased in preca-OLK/OSCC compared to PCA. The use of the IDO1 inhibitor reduced 4NQO induced oral carcinogenesis in mice. Mechanistically, IFN-γ-JAK-STAT pathway was associated with IDO1 upregulation in OLK and OSCC. Conclusions: These results highlight that Macro-IDO1-enriched in preca-OLK possesses a strong immunosuppressive role and contributes to oral carcinogenesis, providing a potential target for preventing precancerous legions from transformation into OSCC.

Wnt5a and Notum Influence the Temporal Dynamics of Cartilaginous Mesenchymal Condensations in Developing Trachea.

The trachea is essential for proper airflow to the lungs for gas exchange. Frequent congenital tracheal malformations affect the cartilage, causing the collapse of the central airway during the respiratory cycle. We have shown that Notum, a Wnt ligand de-acylase that attenuates the canonical branch of the Wnt signaling pathway, is necessary for cartilaginous mesenchymal condensations. In Notum deficient tracheas, chondrogenesis is delayed, and the tracheal lumen is narrowed. It is unknown if Notum attenuates non-canonical Wnt signaling. Notably, we observed premature tracheal chondrogenesis after mesenchymal deletion of the non-canonical Wnt5a ligand. We hypothesize that Notum and Wnt5a are required to mediate the timely formation of mesenchymal condensations, giving rise to the tracheal cartilage. Ex vivo culture of tracheal tissue shows that chemical inhibition of the Wnt non-canonical pathway promotes earlier condensations, while Notum inhibition presents delayed condensations. Furthermore, non-canonical Wnt induction prevents the formation of cartilaginous mesenchymal condensations. On the other hand, cell-cell interactions among chondroblasts increase in the absence of mesenchymal Wnt5a. By performing an unbiased analysis of the gene expression in Wnt5a and Notum deficient tracheas, we detect that mRNA of genes essential for chondrogenesis and extracellular matrix formation are upregulated by E11.5 in Wnt5a mutants. The expression profile supports the premature and delayed chondrogenesis observed in Wnt5a and Notum deficient tracheas, respectively. We conclude that Notum and Wnt5a are necessary for proper tracheal cartilage patterning by coordinating timely chondrogenesis. Thus, these studies shed light on molecular mechanisms underlying congenital anomalies of the trachea.